The deterioration of neuronal cell bodies and connections within the limbic region of the human cortex appears to contribute importantly to Alzheimer's disease. Whereas most previous studies of this contribution have focused on the changes that occur in the hippocampal, entorhinal and associated temporal cortices, recent evidence indicates that the cingulate and subicular cortices display significant alterations in Alzheimer's patients, and in at least some of these cases, the abnormalities occur in the absence of any obvious structural changes in the hippocampus and other limbic regions of cortex. The posterior-most component of the cingulate cortex, i.e., the retrosplenial cortex, appears to be an important area for the integration and transmission of hippocampal information to other cortical regions, including other areas of the cingulate cortex, and this area displays marked deterioration in the aging rat. The present proposal will test the hypothesis that in Alzheimer's patients similar damage to the retrosplenial cortex occurs, damage that would be expected to disconnect the hippocampal formation from thalamic and cortical connections. Specifically, the studies will employ retrosplenial tissue from Alzheimer's patients and age matched controls to test three hypotheses. First, neuritic plaques and neuronal cell loss in the retrosplenial cortex occur in Alzheimer's disease, gradually increase as the disease progresses and are most prominent in supragranular layers of this cortex. Second, Alzheimer's disease results in a decrease in cortical acetylcholine esterase (AChE, indicative of a decline in acetyl choline innervation) and noradrenaline but little change in gamma amino butyric acid immunoreactivity in the retrosplenial cortex. Third, we will use the in vitro slice preparation and the postmortem tracing technique to test the hypothesis that Alzheimer's disease causes a deterioration of supragranular neurons and their connections in the retrosplenial cortex. Together, the results of these experiments will further elucidate the participation of the cingulate cortex in Alzheimer's disease.